Affinage · Plasmodium

MiaA

PF3D7_1207600 · tRNA dimethylallyltransferase, putative

Audit flag: identity unverified
Annotated
2026-09-08
4 papers in source corpus 2 papers cited in narrative 2 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MiaA (PF3D7_1207600) is annotated as the sole isoprenoid-dependent tRNA prenylation enzyme in the P. falciparum apicoplast (PMID:35257658). Genetic knockout of MiaA in blood-stage parasites has no effect on parasite viability or apicoplast biogenesis, establishing that tRNA prenylation by MiaA cannot account for the apicoplast's dependence on IPP synthesis (PMID:35257658). Beyond this dispensability phenotype, no direct biochemical characterization of MiaA itself has been established in the available corpus; its assignment as a tRNA isopentenyltransferase that uses DMAPP to generate the i6A37 modification rests on bacterial orthology rather than direct in vitro demonstration (PMID:35164549).

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2022 Medium

    The field asked whether the apicoplast's reliance on isoprenoid (IPP) synthesis could be explained by tRNA prenylation; deleting the only enzyme carrying out this reaction tested that hypothesis directly.

    Evidence Genetic knockout of MiaA in P. falciparum blood-stage parasites with readouts of parasite growth and apicoplast biogenesis

    PMID:35257658

    Open questions at the time
    • Does not establish MiaA's biochemical activity in P. falciparum
    • Does not identify which IPP-dependent process explains apicoplast reliance on isoprenoid synthesis
    • Phenotype assessed only in blood stage; other life-cycle stages not tested
  2. 2022 Low

    To place MiaA in the tRNA modification pathway, its activity was inferred as the upstream isopentenyltransferase generating i6A37, with MiaB acting downstream to methylthiolate the modification.

    Evidence Pathway inference from bacterial ortholog biochemistry, described in the context of genetic deletion studies of the downstream enzyme MiaB in P. falciparum

    PMID:35164549

    Open questions at the time
    • MiaA enzymatic activity attributed by orthology, not demonstrated in vitro or in P. falciparum
    • tRNA substrates of MiaA not experimentally defined in P. falciparum
    • The finding centers on MiaB; MiaA's own role is only inferred as upstream

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown what biochemical function MiaA performs directly in P. falciparum and, given its dispensability, what IPP-dependent process it might contribute to, if any.
  • No direct demonstration of MiaA tRNA isopentenyltransferase activity
  • No identification of MiaA-modified tRNA substrates in P. falciparum
  • No structural model or partner interaction data for MiaA

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
MIAB (DOWNSTREAM METHYLTHIOLATION ENZYME, PER PATHWAY INFERENCE [#1])

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2022 Knockout of MiaA (PF3D7_1207600), the sole isoprenoid-dependent tRNA prenylation enzyme in the apicoplast, has no effect on blood-stage parasite viability and no effect on apicoplast biogenesis, demonstrating that tRNA prenylation by MiaA cannot explain the apicoplast's reliance on IPP synthesis. Genetic knockout of MiaA in P. falciparum blood-stage parasites with phenotypic readout of parasite growth and apicoplast biogenesis eLife Medium 35257658
2022 MiaA (PF3D7_1207600) acts as a tRNA isopentenyltransferase, using DMAPP to isopentenylate the N6-nitrogen of adenine at base 37 (A37) of a subset of tRNAs that read codons beginning with uridine, generating the i6A37 modification; MiaB acts downstream of MiaA to further methylthiolate this modification. Inference from bacterial ortholog biochemistry and pathway context described in the context of genetic deletion studies of downstream enzyme MiaB in P. falciparum mBio Low 35164549

Source papers

Stage 0 corpus · 4 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2022 Critical role for isoprenoids in apicoplast biogenesis by malaria parasites. eLife 41 35257658
2023 The interdependence of isoprenoid synthesis and apicoplast biogenesis in malaria parasites. PLoS pathogens 0 37883328
2022 Roles of Ferredoxin-Dependent Proteins in the Apicoplast of Plasmodium falciparum Parasites. mBio 0 35164549
2013 The suf iron-sulfur cluster synthesis pathway is required for apicoplast maintenance in malaria parasites. PLoS pathogens 0 24086138